Skip to main content

Advertisement

SpringerLink
Log in

Positron Emission Tomography Imaging of Synaptic Dysfunction in Parkinson’s Disease

  • Review
  • Published:
Neuroscience Bulletin Aims and scope Submit manuscript

Abstract

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases with a complex pathogenesis. Aggregations formed by abnormal deposition of alpha-synuclein (αSyn) lead to synapse dysfunction of the dopamine and non-dopamine systems. The loss of dopaminergic neurons and concomitant alterations in non-dopaminergic function in PD constitute its primary pathological manifestation. Positron emission tomography (PET), as a representative molecular imaging technique, enables the non-invasive visualization, characterization, and quantification of biological processes at cellular and molecular levels. Imaging synaptic function with PET would provide insights into the mechanisms underlying PD and facilitate the optimization of clinical management. In this review, we focus on the synaptic dysfunction associated with the αSyn pathology of PD, summarize various related targets and radiopharmaceuticals, and discuss applications and perspectives of PET imaging of synaptic dysfunction in PD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Brumberg J, Küsters S, Al-Momani E, Marotta G, Cosgrove KP, van Dyck CH. Cholinergic activity and levodopa-induced dyskinesia: A multitracer molecular imaging study. Ann Clin Transl Neurol 2017, 4: 632–639.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Li LX, Li YL, Wu JT, Song JZ, Li XM. Glutamatergic neurons in the caudal zona incerta regulate parkinsonian motor symptoms in mice. Neurosci Bull 2022, 38: 1–15.

    Article  CAS  PubMed  Google Scholar 

  3. Bloem BR, Okun MS, Klein C. Parkinson’s disease. Lancet 2021, 397: 2284–2303.

    Article  CAS  PubMed  Google Scholar 

  4. Tian M, Zuo C, Civelek AC, Carrio I, Watanabe Y, Kang KW, et al. International nuclear medicine consensus on the clinical use of amyloid positron emission tomography in Alzheimer’s disease. Phenomics 2022, 3: 375–389.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Tian M, Civelek AC, Carrio I, Watanabe Y, Kang KW, Murakami K, et al. International consensus on the use of tau PET imaging agent 18F-flortaucipir in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 2022, 49: 895–904.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Tian M, Watanabe Y, Kang KW, Murakami K, Chiti A, Carrio I, et al. International consensus on the use of[18F]-FDG PET/CT in pediatric patients affected by epilepsy. Eur J Nucl Med Mol Imag 2021, 48: 3827–3834.

    Article  Google Scholar 

  7. Wassouf Z, Schulze-Hentrich JM. Alpha-synuclein at the nexus of genes and environment: the impact of environmental enrichment and stress on brain health and disease. J Neurochem 2019, 150: 591–604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Uchihara T, Giasson BI. Propagation of alpha-synuclein pathology: Hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies. Acta Neuropathol 2016, 131: 49–73.

    Article  CAS  PubMed  Google Scholar 

  9. Haque ME, Akther M, Azam S, Kim IS, Lin Y, Lee YH, et al. Targeting α-synuclein aggregation and its role in mitochondrial dysfunction in Parkinson’s disease. Br J Pharmacol 2022, 179: 23–45.

    Article  CAS  PubMed  Google Scholar 

  10. Wang C, Yang T, Liang M, Xie J, Song N. Astrocyte dysfunction in Parkinson’s disease: from the perspectives of transmitted α-synuclein and genetic modulation. Transl Neurodegener 2021, 10: 39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Rostami J, Mothes T, Kolahdouzan M, Eriksson O, Moslem M, Bergström J, et al. Crosstalk between astrocytes and microglia results in increased degradation of α-synuclein and amyloid-β aggregates. J Neuroinflammation 2021, 18: 124.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 1997, 276: 2045–2047.

    Article  CAS  PubMed  Google Scholar 

  13. Krüger R, Kuhn W, Müller T, Woitalla D, Graeber M, Kösel S, et al. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson’s disease. Nat Genet 1998, 18: 106–108.

    Article  PubMed  Google Scholar 

  14. Kaide S, Watanabe H, Shimizu Y, Iikuni S, Nakamoto Y, Hasegawa M, et al. Identification and evaluation of bisquinoline scaffold as a new candidate for α-synuclein-PET imaging. ACS Chem Neurosci 2020, 11: 4254–4261.

    Article  CAS  PubMed  Google Scholar 

  15. Kuebler L, Buss S, Leonov A, Ryazanov S, Schmidt F, Maurer A, et al. 11C]MODAG-001-towards a PET tracer targeting α-synuclein aggregates. Eur J Nucl Med Mol Imaging 2021, 48: 1759–1772.

    Article  CAS  PubMed  Google Scholar 

  16. Xiang J, Tao Y, Xia Y, Luo S, Zhao Q, Li B, et al. Development of an α-synuclein positron emission tomography tracer for imaging synucleinopathies. Cell 2023, 186: 3350-3367.e19.

    Article  CAS  PubMed  Google Scholar 

  17. González-Rodríguez P, Zampese E, Stout KA, Guzman JN, Ilijic E, Yang B, et al. Disruption of mitochondrial complex I induces progressive Parkinsonism. Nature 2021, 599: 650–656.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  18. Chondrogiannis S, Marzola MC, Rubello D. 18F-DOPA PET/computed tomography imaging. PET Clin 2014, 9: 307–321.

    Article  PubMed  Google Scholar 

  19. Chondrogiannis S, Marzola MC, Al-Nahhas A, Venkatanarayana TD, Mazza A, Opocher G, et al. Normal biodistribution pattern and physiologic variants of 18F-DOPA PET imaging. Nucl Med Commun 2013, 34: 1141–1149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Nandhagopal R, Kuramoto L, Schulzer M, Mak E, Cragg J, McKenzie J, et al. Longitudinal evolution of compensatory changes in striatal dopamine processing in Parkinson’s disease. Brain 2011, 134: 3290–3298.

    Article  PubMed  Google Scholar 

  21. Neves ÂCB, Hrynchak I, Fonseca I, Alves VHP, Pereira MM, Falcão A, et al. Advances in the automated synthesis of 6-[18F]Fluoro-L-DOPA. EJNMMI Radiopharm Chem 2021, 6: 11.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Henry JP, Scherman D. Radioligands of the vesicular monoamine transporter and their use as markers of monoamine storage vesicles. Biochem Pharmacol 1989, 38: 2395–2404.

    Article  CAS  PubMed  Google Scholar 

  23. Cho SS, Christopher L, Koshimori Y, Li C, Lang AE, Houle S, et al. Decreased pallidal vesicular monoamine transporter type 2 availability in Parkinson’s disease: the contribution of the nigropallidal pathway. Neurobiol Dis 2019, 124: 176–182.

    Article  CAS  PubMed  Google Scholar 

  24. Kilbourn MR, Koeppe RA. Classics in neuroimaging: radioligands for the vesicular monoamine transporter 2. ACS Chem Neurosci 2019, 10: 25–29.

    Article  CAS  PubMed  Google Scholar 

  25. Hsiao IT, Weng YH, Hsieh CJ, Lin WY, Wey SP, Kung MP, et al. Correlation of Parkinson disease severity and 18F-DTBZ positron emission tomography. JAMA Neurol 2014, 71: 758–766.

    Article  PubMed  Google Scholar 

  26. Jiang D, Kong Y, Ren S, Cai H, Zhang Z, Huang Z, et al. Decreased striatal vesicular monoamine transporter 2 (VMAT2) expression in a type 1 diabetic rat model: a longitudinal study using micro-PET/CT. Nucl Med Biol 2020, 82(83): 89–95.

    Article  PubMed  Google Scholar 

  27. Rinne JO, Laihinen A, Någren K, Ruottinen H, Ruotsalainen U, Rinne UK. PET examination of the monoamine transporter with[11C]beta-CIT and[11C]beta-CFT in early Parkinson’s disease. Synapse 1995, 21: 97–103.

    Article  CAS  PubMed  Google Scholar 

  28. Lundkvist C, Halldin C, Swahn CG, Hall H, Karlsson P, Nakashima Y, et al. O-methyl-11C]beta-CIT-FP, a potential radioligand for quantitation of the dopamine transporter: preparation, autoradiography, metabolite studies, and positron emission tomography examinations. Nucl Med Biol 1995, 22: 905–913.

    Article  CAS  PubMed  Google Scholar 

  29. Hall H, Halldin C, Guilloteau D, Chalon S, Emond P, Besnard J, et al. Visualization of the dopamine transporter in the human brain postmortem with the new selective ligand[125I]PE2I. NeuroImage 1999, 9: 108–116.

    Article  CAS  PubMed  Google Scholar 

  30. Shetty HU, Zoghbi SS, Liow JS, Ichise M, Hong J, Musachio JL, et al. Identification and regional distribution in rat brain of radiometabolites of the dopamine transporter PET radioligand[11C]PE2I. Eur J Nucl Med Mol Imaging 2007, 34: 667–678.

    Article  CAS  PubMed  Google Scholar 

  31. Varrone A, Tóth M, Steiger C, Takano A, Guilloteau D, Ichise M, et al. Kinetic analysis and quantification of the dopamine transporter in the nonhuman primate brain with 11C-PE2I and 18F-FE-PE2I. J Nucl Med 2011, 52: 132–139.

    Article  CAS  PubMed  Google Scholar 

  32. Varrone A, Steiger C, Schou M, Takano A, Finnema SJ, Guilloteau D, et al. In vitro autoradiography and in vivo evaluation in cynomolgus monkey of[18F]FE-PE2I, a new dopamine transporter PET radioligand. Synapse 2009, 63: 871–880.

    Article  CAS  PubMed  Google Scholar 

  33. Volkow ND, Fowler JS, Logan J, Alexoff D, Zhu W, Telang F, et al. Effects of modafinil on dopamine and dopamine transporters in the male human brain: clinical implications. JAMA 2009, 301: 1148–1154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Olsson H, Halldin C, Swahn CG, Farde L. Quantification of[11C]FLB 457 binding to extrastriatal dopamine receptors in the human brain. J Cereb Blood Flow Metab 1999, 19: 1164–1173.

    Article  CAS  PubMed  Google Scholar 

  35. Ceccarini J, Vrieze E, Koole M, Muylle T, Bormans G, Claes S, et al. Optimized in vivo detection of dopamine release using 18F-fallypride PET. J Nucl Med 2012, 53: 1565–1572.

    Article  PubMed  Google Scholar 

  36. Narendran R, Mason NS, Laymon CM, Lopresti BJ, Velasquez ND, May MA, et al. A comparative evaluation of the dopamine D(2/3) agonist radiotracer[11C](-)-N-propyl-norapomorphine and antagonist[11C]raclopride to measure amphetamine-induced dopamine release in the human striatum. J Pharmacol Exp Ther 2010, 333: 533–539.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wilson AA, McCormick P, Kapur S, Willeit M, Garcia A, Hussey D, et al. Radiosynthesis and evaluation of[11C]-(+)-4-propyl-3, 4, 4a, 5, 6, 10b-hexahydro-2H-naphtho[1, 2-b][1, 4]oxazin-9-ol as a potential radiotracer for in vivo imaging of the dopamine D2 high-affinity state with positron emission tomography. J Med Chem 2005, 48: 4153–4160.

    Article  CAS  PubMed  Google Scholar 

  38. Vercouillie J, Buron F, Sérrière S, Rodrigues N, Gulhan Z, Chartier A, et al. Development and preclinical evaluation of[18F]FBVM as a new potent PET tracer for vesicular acetylcholine transporter. Eur J Med Chem 2022, 244: 114794.

    Article  CAS  PubMed  Google Scholar 

  39. Nordberg A, Hartvig P, Lilja A, Viitanen M, Amberla K, Lundqvist H, et al. Decreased uptake and binding of 11C-nicotine in brain of Alzheimer patients as visualized by positron emission tomography. J Neural Transm Park Dis Dement Sect 1990, 2: 215–224.

    Article  CAS  PubMed  Google Scholar 

  40. Sihver W, Fasth KJ, Ogren M, Lundqvist H, Bergström M, Watanabe Y, et al. In vivo positron emission tomography studies on the novel nicotinic receptor agonist[11C]MPA compared with[11C]ABT-418 and (S) (-)[11C]nicotine in rhesus monkeys. Nucl Med Biol 1999, 26: 633–640.

    Article  CAS  PubMed  Google Scholar 

  41. Valette H, Bottlaender M, Dollé F, Guenther I, Fuseau C, Coulon C, et al. Imaging central nicotinic acetylcholine receptors in baboons with[18F]fluoro-A-85380. J Nucl Med 1999, 40: 1374–1380.

    CAS  PubMed  Google Scholar 

  42. Sabri O, Becker GA, Meyer PM, Hesse S, Wilke S, Graef S, et al. First-in-human PET quantification study of cerebral α4β2* nicotinic acetylcholine receptors using the novel specific radioligand (-)-[(18)F]Flubatine. NeuroImage 2015, 118: 199–208.

    Article  CAS  PubMed  Google Scholar 

  43. Wong DF, Kuwabara H, Kim J, Brasic JR, Chamroonrat W, Gao Y, et al. PET imaging of high-affinity α4β2 nicotinic acetylcholine receptors in humans with 18F-AZAN, a radioligand with optimal brain kinetics. J Nucl Med 2013, 54: 1308–1314.

    Article  CAS  PubMed  Google Scholar 

  44. Kilbourn MR, Snyder SE, Sherman PS, Kuhl DE. In vivo studies of acetylcholinesterase activity using a labeled substrate, N-[11C]methylpiperdin-4-yl propionate ([11C]PMP). Synapse 1996, 22: 123–131.

    Article  CAS  PubMed  Google Scholar 

  45. Gjerløff T, Jakobsen S, Nahimi A, Munk OL, Bender D, Alstrup AKO, et al. In vivo imaging of human acetylcholinesterase density in peripheral organs using 11C-donepezil: dosimetry, biodistribution, and kinetic analyses. J Nucl Med 2014, 55: 1818–1824.

    Article  PubMed  Google Scholar 

  46. Hiraoka K, Okamura N, Funaki Y, Watanuki S, Tashiro M, Kato M, et al. Quantitative analysis of donepezil binding to acetylcholinesterase using positron emission tomography and[5-(11)C-methoxy]donepezil. NeuroImage 2009, 46: 616–623.

    Article  PubMed  Google Scholar 

  47. de Natale ER, Wilson H, Politis M. Serotonergic imaging in Parkinson’s disease. Prog Brain Res 2021, 261: 303–338.

    Article  PubMed  Google Scholar 

  48. Kish SJ, Tong J, Hornykiewicz O, Rajput A, Chang LJ, Guttman M, et al. Preferential loss of serotonin markers in caudate versus putamen in Parkinson’s disease. Brain 2008, 131: 120–131.

    PubMed  Google Scholar 

  49. Wersinger C, Rusnak M, Sidhu A. Modulation of the trafficking of the human serotonin transporter by human alpha-synuclein. Eur J Neurosci 2006, 24: 55–64.

    Article  PubMed  Google Scholar 

  50. Pagano G, Niccolini F, Politis M. The serotonergic system in Parkinson’s patients with dyskinesia: evidence from imaging studies. J Neural Transm 2018, 125: 1217–1223.

    Article  CAS  PubMed  Google Scholar 

  51. Fu JF, Matarazzo M, McKenzie J, Neilson N, Vafai N, Dinelle K, et al. Serotonergic system impacts levodopa response in early Parkinson’s and future risk of dyskinesia. Mov Disord 2021, 36: 389–397.

    Article  CAS  PubMed  Google Scholar 

  52. Joling M, van den Heuvel OA, Berendse HW, Booij J, Vriend C. Serotonin transporter binding and anxiety symptoms in Parkinson’s disease. J Neurol Neurosurg Psychiatry 2018, 89: 89–94.

    Article  PubMed  Google Scholar 

  53. Prange S, Metereau E, Maillet A, Klinger H, Schmitt E, Lhommée E, et al. Limbic serotonergic plasticity contributes to the compensation of apathy in early Parkinson’s disease. Mov Disord 2022, 37: 1211–1221.

    Article  CAS  PubMed  Google Scholar 

  54. Parsey RV, Kegeles LS, Hwang DR, Simpson N, Abi-Dargham A, Mawlawi O, et al. In vivo quantification of brain serotonin transporters in humans using[11C]McN 5652. J Nucl Med 2000, 41: 1465–1477.

    CAS  PubMed  Google Scholar 

  55. Szabo Z, McCann UD, Wilson AA, Scheffel U, Owonikoko T, Mathews WB, et al. Comparison of (+)-(11)C-McN5652 and (11)C-DASB as serotonin transporter radioligands under various experimental conditions. J Nucl Med 2002, 43: 678–692.

    CAS  PubMed  Google Scholar 

  56. Huang Y, Hwang DR, Narendran R, Sudo Y, Chatterjee R, Bae SA, et al. Comparative evaluation in nonhuman Primates of five PET radiotracers for imaging the serotonin transporters: [11C]McN 5652, [11C]ADAM, [11C]DASB, [11C]DAPA, and[11C]AFM. J Cereb Blood Flow Metab 2002, 22: 1377–1398.

    Article  CAS  PubMed  Google Scholar 

  57. Walker M, Ehrlichmann W, Stahlschmidt A, Pichler BJ, Fischer K. In vivo evaluation of 11C-DASB for quantitative SERT imaging in rats and mice. J Nucl Med 2016, 57: 115–121.

    Article  CAS  PubMed  Google Scholar 

  58. Doder M, Rabiner EA, Turjanski N, Lees AJ, Brooks DJ, Study 1W 1P. Tremor in Parkinson’s disease and serotonergic dysfunction: An 11C-WAY 100635 PET study. Neurology 2003, 60: 601–605.

    Article  CAS  PubMed  Google Scholar 

  59. Tipre DN, Zoghbi SS, Liow JS, Green MV, Seidel J, Ichise M, et al. PET imaging of brain 5-HT1A receptors in rat in vivo with 18F-FCWAY and improvement by successful inhibition of radioligand defluorination with miconazole. J Nucl Med 2006, 47: 345–353.

    CAS  PubMed  Google Scholar 

  60. Hillmer AT, Wooten DW, Bajwa AK, Higgins AT, Lao PJ, Betthauser TJ, et al. First-in-human evaluation of 18F-mefway, a PET radioligand specific to serotonin-1A receptors. J Nucl Med 2014, 55: 1973–1979.

    Article  CAS  PubMed  Google Scholar 

  61. Choi JY, Lyoo CH, Kim JS, Kim KM, Kang JH, Choi SH, et al. 18F-Mefway PET imaging of serotonin 1A receptors in humans: a comparison with 18F-FCWAY. PLoS One 2015, 10: e0121342.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Sommerauer M, Fedorova TD, Hansen AK, Knudsen K, Otto M, Jeppesen J, et al. Evaluation of the noradrenergic system in Parkinson’s disease: an 11C-MeNER PET and neuromelanin MRI study. Brain 2018, 141: 496–504.

    Article  PubMed  Google Scholar 

  63. Severance AJ, Milak MS, Kumar JSD, Prabhakaran J, Majo VJ, Simpson NR, et al. In vivo assessment of[11C]MRB as a prospective PET ligand for imaging the norepinephrine transporter. Eur J Nucl Med Mol Imaging 2007, 34: 688–693.

    Article  CAS  PubMed  Google Scholar 

  64. Takano A, Halldin C, Farde L. SERT and NET occupancy by venlafaxine and milnacipran in nonhuman Primates: a PET study. Psychopharmacology 2013, 226: 147–153.

    Article  CAS  PubMed  Google Scholar 

  65. Vase KH, Peters D, Nielsen EØ, Alstrup AKO, Bender D. 11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter. Nucl Med Biol 2014, 41: 758–764.

    Article  CAS  PubMed  Google Scholar 

  66. Hou L, Rong J, Haider A, Ogasawara D, Varlow C, Schafroth MA, et al. Positron emission tomography imaging of the endocannabinoid system: Opportunities and challenges in radiotracer development. J Med Chem 2021, 64: 123–149.

    Article  CAS  PubMed  Google Scholar 

  67. Burns HD, Van Laere K, Sanabria-Bohórquez S, Hamill TG, Bormans G, Eng WS, et al. 18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor. Proc Natl Acad Sci U S A 2007, 104: 9800–9805.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  68. Lahdenpohja S, Rajala NA, Helin JS, Haaparanta-Solin M, Solin O, López-Picón FR, et al. Ruthenium-mediated 18F-fluorination and preclinical evaluation of a new CB1 receptor imaging agent[18F]FPATPP. ACS Chem Neurosci 2020, 11: 2009–2018.

    Article  CAS  PubMed  Google Scholar 

  69. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 2015, 30: 1591–1601.

    Article  PubMed  Google Scholar 

  70. Stormezand GN, Chaves LT, Vállez García D, Doorduin J, De Jong BM, Leenders KL, et al. Intrastriatal gradient analyses of 18F-FDOPA PET scans for differentiation of Parkinsonian disorders. Neuroimage Clin 2020, 25: 102161.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Palermo G, Ceravolo R. Molecular imaging of the dopamine transporter. Cells 2019, 8: 872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Mo SJ, Axelsson J, Jonasson L, Larsson A, Ögren MJ, Ögren M, et al. Dopamine transporter imaging with[18f]fe-pe2i pet and[123i]fp-cit spect-a clinical comparison. EJNMMI Res 2018, 8: 100.

    Article  Google Scholar 

  73. Delva A, Van Weehaeghe D, van Aalst J, Ceccarini J, Koole M, Baete K, et al. Quantification and discriminative power of 18F-FE-PE2I PET in patients with Parkinson’s disease. Eur J Nucl Med Mol Imaging 2020, 47: 1913–1926.

    Article  CAS  PubMed  Google Scholar 

  74. Lee CS, Samii A, Sossi V, Ruth TJ, Schulzer M, Holden JE, et al. In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson’s disease. Ann Neurol 2000, 47: 493–503.

    Article  CAS  PubMed  Google Scholar 

  75. Liu XL, Liu SY, Barret O, Tamagnan GD, Qiao HW, Song TB, et al. Diagnostic value of striatal 18F-FP-DTBZ PET in Parkinson’s disease. Front Aging Neurosci 2022, 14: 931015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Cheon M, Kim SM, Ha SW, Kang MJ, Yang HE, Yoo J. Diagnostic performance for differential diagnosis of atypical parkinsonian syndromes from Parkinson’s disease using quantitative indices of 18F-FP-CIT PET/CT. Diagnostics 2022, 12: 1402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Zhao Y, Wu P, Wu J, Brendel M, Lu J, Ge J, et al. Decoding the dopamine transporter imaging for the differential diagnosis of Parkinsonism using deep learning. Eur J Nucl Med Mol Imaging 2022, 49: 2798–2811.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Appel L, Jonasson M, Danfors T, Nyholm D, Askmark H, Lubberink M, et al. Use of 11C-PE2I PET in differential diagnosis of parkinsonian disorders. J Nucl Med 2015, 56: 234–242.

    Article  PubMed  Google Scholar 

  79. Chou KL, Dayalu P, Koeppe RA, Gilman S, Spears CC, Albin RL, et al. Serotonin transporter imaging in multiple system atrophy and Parkinson’s disease. Mov Disord 2022, 37: 2301–2307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Shinotoh H, Namba H, Yamaguchi M, Fukushi K, Nagatsuka S, Iyo M, et al. Positron emission tomographic measurement of acetylcholinesterase activity reveals differential loss of ascending cholinergic systems in Parkinson’s disease and progressive supranuclear palsy. Ann Neurol 1999, 46: 62–69.

    Article  CAS  PubMed  Google Scholar 

  81. Gilman S, Koeppe RA, Nan B, Wang CN, Wang X, Junck L, et al. Cerebral cortical and subcortical cholinergic deficits in parkinsonian syndromes. Neurology 2010, 74: 1416–1423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Kerstens VS, Fazio P, Sundgren M, Brumberg J, Halldin C, Svenningsson P, et al. Longitudinal DAT changes measured with[18F]FE-PE2I PET in patients with Parkinson’s disease; a validation study. NeuroImage Clin 2023, 37: 103347.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kumar A, Mann S, Sossi V, Ruth TJ, Stoessl AJ, Schulzer M, et al. 11C]DTBZ-PET correlates of levodopa responses in asymmetric Parkinson’s disease. Brain 2003, 126: 2648–2655.

    Article  PubMed  Google Scholar 

  84. Boertien JM, van der Zee S, Chrysou A, Gerritsen MJJ, Jansonius NM, Spikman JM, et al. Study protocol of the DUtch PARkinson Cohort (DUPARC): a prospective, observational study of de novo Parkinson’s disease patients for the identification and validation of biomarkers for Parkinson’s disease subtypes, progression and pathophysiology. BMC Neurol 2020, 20: 245.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Gjerløff T, Fedorova T, Knudsen K, Munk OL, Nahimi A, Jacobsen S, et al. Imaging acetylcholinesterase density in peripheral organs in Parkinson’s disease with 11C-donepezil PET. Brain 2015, 138: 653–663.

    Article  PubMed  Google Scholar 

  86. Knudsen K, Fedorova TD, Hansen AK, Sommerauer M, Otto M, Svendsen KB, et al. In-vivo staging of pathology in REM sleep behaviour disorder: a multimodality imaging case-control study. Lancet Neurol 2018, 17: 618–628.

    Article  PubMed  Google Scholar 

  87. Horsager J, Andersen KB, Knudsen K, Skjærbæk C, Fedorova TD, Okkels N, et al. Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study. Brain 2020, 143: 3077–3088.

    Article  PubMed  Google Scholar 

  88. Son HJ, Oh JS, Oh M, Lee SJ, Oh SJ, Chung SJ, et al. Test-retest reproducibility of dopamine transporter density measured with[18F]FP-CIT PET in patients with essential tremor and Parkinson’s disease. Ann Nucl Med 2021, 35: 299–306.

    Article  CAS  PubMed  Google Scholar 

  89. Choi BW, Kang S, Kim HW, Kwon OD, Vu HD, Youn SW. Faster region-based convolutional neural network in the classification of different Parkinsonism patterns of the Striatum on maximum intensity projection images of[18F]FP-CIT positron emission tomography. Diagnostics 2021, 11: 1557.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Sun X, Ge J, Li L, Zhang Q, Lin W, Chen Y, et al. Use of deep learning-based radiomics to differentiate Parkinson’s disease patients from normal controls: a study based on[18F]FDG PET imaging. Eur Radiol 2022, 32: 8008–8018.

    Article  CAS  PubMed  Google Scholar 

  91. Tian M, He X, Jin C, He X, Wu S, Zhou R, et al. Transpathology: Molecular imaging-based pathology. Eur J Nucl Med Mol Imaging 2021, 48: 2338–2350.

    Article  PubMed  PubMed Central  Google Scholar 

  92. DaSilva JN, Kilbourn MR. In vivo binding of[11C]tetrabenazine to vesicular monoamine transporters in mouse brain. Life Sci 1992, 51: 593–600.

    Article  CAS  PubMed  Google Scholar 

  93. Kilbourn MR, Sherman PS, Abbott LC. Mutant mouse strains as models for in vivo radiotracer evaluations: [11C]methoxytetrabenazine ([11C]MTBZ) in tottering mice. Nucl Med Biol 1995, 22: 565–567.

    Article  CAS  PubMed  Google Scholar 

  94. Bohnen NI, Kanel P, Müller MLTM. Molecular imaging of the cholinergic system in Parkinson’s disease. Int Rev Neurobiol 2018, 141: 211–250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Rogers GA, Stone-Elander S, Ingvar M, Eriksson L, Parsons SM, Widén L. 18F-labelled vesamicol derivatives: syntheses and preliminary in vivo small animal positron emission tomography evaluation. Nucl Med Biol 1994, 21: 219–230.

    Article  CAS  PubMed  Google Scholar 

  96. Gage HD, Voytko ML, Ehrenkaufer RL, Tobin JR, Efange SM, Mach RH. Reproducibility of repeated measures of cholinergic terminal density using. J Nucl Med 2000, 41: 2069–2076.

    CAS  PubMed  Google Scholar 

  97. Coughlin JM, Slania S, Du Y, Rosenthal HB, Lesniak WG, Minn I, et al. 18F-XTRA PET for enhanced imaging of the extrathalamic α4β2 nicotinic acetylcholine receptor. J Nucl Med 2018, 59: 1603–1608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Horti AG, Gao Y, Kuwabara H, Wang Y, Abazyan S, Yasuda RP, et al. 18F-ASEM, a radiolabeled antagonist for imaging the α7-nicotinic acetylcholine receptor with PET. J Nucl Med 2014, 55: 672–677.

    Article  CAS  PubMed  Google Scholar 

  99. Aznavour N, Zimmer L. 18F]MPPF as a tool for the in vivo imaging of 5-HT1A receptors in animal and human brain. Neuropharmacology 2007, 52: 695–707.

    Article  CAS  PubMed  Google Scholar 

  100. Horti AG, Fan H, Kuwabara H, Hilton J, Ravert HT, Holt DP, et al. 11C-JHU75528: a radiotracer for PET imaging of CB1 cannabinoid receptors. J Nucl Med 2006, 47: 1689–1696.

    CAS  PubMed  Google Scholar 

  101. Borgan F, Laurikainen H, Veronese M, Marques TR, Haaparanta-Solin M, Solin O, et al. In vivo availability of cannabinoid 1 receptor levels in patients with first-episode psychosis. JAMA Psychiatry 2019, 76: 1074–1084.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Wilson H, Dervenoulas G, Pagano G, Koros C, Yousaf T, Picillo M, et al. Serotonergic pathology and disease burden in the premotor and motor phase of A53T α-synuclein Parkinsonism: a cross-sectional study. Lancet Neurol 2019, 18: 748–759.

    Article  CAS  PubMed  Google Scholar 

  103. Nahimi A, Sommerauer M, Kinnerup MB, Østergaard K, Winterdahl M, Jacobsen J, et al. Noradrenergic deficits in parkinson disease imaged with 11C-MeNER. J Nucl Med 2018, 59: 659–664.

    Article  CAS  PubMed  Google Scholar 

  104. Wang J, Zuo CT, Jiang YP, Guan YH, Chen ZP, Xiang JD, et al. 18F-FP-CIT PET imaging and SPM analysis of dopamine transporters in Parkinson’s disease in various Hoehn & Yahr stages. J Neurol 2007, 254: 185–190.

    Article  CAS  PubMed  Google Scholar 

  105. Oh M, Lee N, Kim C, Son HJ, Sung C, Oh SJ, et al. Diagnostic accuracy of dual-phase 18F-FP-CIT PET imaging for detection and differential diagnosis of Parkinsonism. Sci Rep 2021, 11: 14992.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This review was supported by the National Key Research and Development Program of China (2022YFC2009900, 2021YFE0108300, 2022YFE0118000, and 2021YFA1101700), the National Natural Science Foundation of China (82030049), and Fundamental Research Funds for the Central Universities of China.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China

    Jiaqi Niu, Yan Zhong, Chentao Jin, Peili Cen, Jing Wang, Chunyi Cui, Le Xue, Xingyue Cui, Mei Tian & Hong Zhang

  2. Institute of Nuclear Medicine and Molecular Imaging, Zhejiang University, Hangzhou, 310009, China

    Jiaqi Niu, Yan Zhong, Chentao Jin, Peili Cen, Jing Wang, Chunyi Cui, Le Xue, Xingyue Cui, Mei Tian & Hong Zhang

  3. Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, 310009, China

    Jiaqi Niu, Yan Zhong, Chentao Jin, Peili Cen, Jing Wang, Chunyi Cui, Le Xue, Xingyue Cui, Mei Tian & Hong Zhang

  4. College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, 310014, China

    Hong Zhang

  5. Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, 310014, China

    Hong Zhang

  6. Huashan Hospital and Human Phenome Institute, Fudan University, Shanghai, 200040, China

    Mei Tian

Authors
  1. Jiaqi Niu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chentao Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peili Cen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chunyi Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Le Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xingyue Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mei Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Mei Tian or Hong Zhang.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Niu, J., Zhong, Y., Jin, C. et al. Positron Emission Tomography Imaging of Synaptic Dysfunction in Parkinson’s Disease. Neurosci. Bull. (2024). https://doi.org/10.1007/s12264-024-01188-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12264-024-01188-0

Keywords

Search

Navigation